Pelletization is the agglomeration of active ingredients and excipients in the form of spherical beads called pellets. With respect to the preferred embodiment of the present invention, pharmaceutical pellets have numerous pharmacokinetic and biopharmaceutical advantages over single dosage units such as tablets. Moreover, they provide a viable alternative for blending incompatible active ingredients, obtaining different release profiles and development of multi-drug controlled release formulations. As a result of these flexibilities, use of pellets in oral drug delivery systems has been growing steadily over last few years and pelletization has become a multi-million dollar industry.
Pellets are prepared on an industrial scale by extrusion-spheronization, high speed shear mixers, drug layering using coating pans and fluidized bed equipment and cryopelletization. All these methods require very specific and expensive equipment and highly skilled staff. In addition, process development and validation of these techniques is a tedious procedure. The present invention presents a simple and new technique for producing pellets with varying properties for multiple commercial uses.
The concept of dropping liquids/molten liquids as droplets into a cooling fluid and thereby freezing/solidifying them into pellets is known in the art. The cooling fluid usually used is typically either a liquid nitrogen or cooling gases from liquid nitrogen. The most widely used process for producing solid particles is called ‘spray congealing’, where molten solid mass is dropped/sprayed into cooling chambers/cooling towers. This process may not be suitable for solids which have long crystallization temperatures and also for solids which exhibit supercooling like sugars. Accordingly, the height of these prior art towers will need to be high, and they can be as high as 100 meters. Embodiments of the present invention will not require towers of that height. Moreover this prior art process may impart surface irregularities, and the pellets may not be spherical in shape.
In another technique, called ‘cryopelletization’, aqueous/organic solutions or suspensions or emulsions are dropped into liquid nitrogen to get frozen particles. These particles are further freeze dried/lyophilized to remove water/organic solvents. Liquid nitrogen has a temperature of about −196° C., which is difficult to handle. The droplets which are liquids/semisolids can lose their shape upon impact with the liquid nitrogen, therefore, surface irregularities may be present and they may not be in spherical shape.
U.S. Pat. No. 6,074,581 discloses a method of making prills that comprises injecting a prill-forming composition into a liquid. The liquid is in turbulent flow when the mixture is injected so as to break up the prill mixture into small droplets and to separate them during subsequent cooling and solidification. This turbulent flow makes pellet uniformity more difficult to obtain.
U.S. Pat. No. 4,470,202 describes a method of making spherical pellets comprising introducing a liquid pellet medium into a column liquid in the form of droplets and collecting frozen pellets at the top of a column. The present invention achieves greater flexibility in pellet size control, shape, and size distribution.
The present invention overcomes deficiencies described in the prior art.